Avril 2017

« Susceptibility to intestinal infection: how host genes and diet control outcome in the C. rodentium mouse model »

Samantha GRUENHEID (McGill University Canada) (invited by S. Salcedo)

Citrobacter rodentium is an intestinal pathogen of mice widely used to model enteropathogenic and enterohemorrhagic E. coli infection in humans. While C. rodentium causes self-limiting colitis in most inbred mouse strains, it induces fatal diarrhea in susceptible mice. We used a forward genetic approach to identify the R-spondin2 gene (Rspo2) as a major determinant of susceptibility to C. rodentium infection in mice. Robust induction of Rspo2 expression during infection in susceptible mouse strains causes an uncontrolled WNT-mediated proliferative response in the intestinal epithelium, leading to the generation of a poorly differentiated colonic epithelium, intestinal dysfunction, and animal death. More recently we have found that this genetic susceptibility can be mitigated by diet. Our current studies are aimed a better understanding of the molecular details underlying these effects.

Salle de Conférences IBCP

Lundi
10 / 04 / 2017
11h00

«The oxytocin system in a neurodevelopment imprinted disease with autism spectrum disorders»

Methionine sulfoxide reductases (Msrs) represent an important class of antioxidant repair enzymes that catalyse the thioredoxin-dependent reduction of methionine sulfoxide back to methionine. In vivo, the role of Msrs is described as essential in protecting cells against oxidative damages, and to play a role in virulence of pathogenic Neisseriae. There exist different structurally-unrelated classes of Msrs which present different substrate specificities but a similar new and original catalytic mechanism implying the sulfenic acid chemistry. A scenario, in particular of the reductase step, common to all Msrs will be presented and discussed in terms of catalysis and evolution. The periplasmic complex thiol-redox relay system involved, in Neisseria meningitidis, in Msrs recycling activities but also in bacterial survival will also be presented